AB0109 INCREASED NEUTROPHIL FREQUENCY IN LYMPH NODES OF PATIENTS WITH PSORIATIC ARTHRITIS

Abstract

BackgroundIncreased presence of neutrophils in the skin1, synovium2,3, and entheses4 of patients with Psoriatic Arthritis (PsA) and their downregulation upon successful treatment2,5,6, suggests a role for neutrophils in PsA pathogenesis. As neutrophils have been implicated in Th17 differentiation, gaining insight in the presence and function of neutrophils within lymph nodes, which are the epicentre of T cell activation and differentiation, could be important in unravelling disease pathogenesis.ObjectivesWe hypothesize that activated neutrophils migrate from inflamed peripheral tissues to lymph nodes, where they steer inflammation by interaction with tissue resident cells and immune cells, ultimately resulting in activation of IL-17 producing T cells. To investigate this, we studied the presence of neutrophils in lymph node biopsies of patients with inflammatory arthritis, including PsA, and compared their frequencies to controls.MethodsTen PsA patients, 34 seropositive individuals at risk of developing rheumatoid arthritis (RA-risk), 26 ACPA- RA patients and 10 healthy controls (HC) underwent ultrasound-guided inguinal lymph node biopsy. These biobanked biopsies were analysed using qPCR and immunohistochemistry. Flow cytometry on fresh biopsies was used to determine cell frequencies in six active PsA patients (defined as arthritis in ≥1 joint) and two RA-risk individuals.ResultsqPCR analyses showed significantly increased mRNA levels of Cathepsin G (CTSG), which is highly expressed by neutrophils, in PsA patients compared to HC (p = 0.020). Immunohistochemistry showed that the neutrophil marker CD15 is significantly increased in PsA patients compared to HC (p = 0.008). Preliminary flow cytometry analyses indicates a clear population of CD45+CD16+CD66b+ neutrophils in lymph node biopsies of PsA patients while this was not observed in RA-risk individuals.ConclusionOverall, we show for the first time an increased presence of neutrophils in lymph nodes of PsA patients when compared to controls. Future studies are needed to investigate their functional role in immunoregulation within lymph node organs.References[1]Biasi D, Carletto A, Caramaschi P, et al. Neutrophil functions and IL-8 in psoriatic arthritis and in cutaneous psoriasis. Inflammation. 1998;22(5):533-543.[2]van Mens LJJ, van de Sande MGH, Menegatti S, et al. Brief Report: Interleukin-17 Blockade With Secukinumab in Peripheral Spondyloarthritis Impacts Synovial Immunopathology Without Compromising Systemic Immune Responses. Arthritis Rheumatol. 2018;70(12):1994-2002.[3]Kruithof E, Baeten D, De Rycke L, et al. Synovial histopathology of psoriatic arthritis, both oligo- and polyarticular, resembles spondyloarthropathy more than it does rheumatoid arthritis. Arthritis Res Ther. 2005;7(3).[4]Stavre Z, Bridgewood C, Zhou Q, Maeda Y, Karman J, McGonagle D GE. The Role for Neutrophils in the Early Phases of Enthesitis in Spondyloarthritis [abstract]. Arthritis Rheumatol. 2020;72(July):supple10.[5]Baeten D, Kruithof E, Van Bosch F Den, et al. Immunomodulatory effects of anti-tumor necrosis factor α therapy on synovium in spondylarthropathy: Histologic findings in eight patients from an open-label pilot study. Arthritis Rheum. 2001;44(1):186-195.[6]Van Kuijk AWR, Gerlag DM, Vos K, et al. A prospective, randomised, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: Effects of adalimumab treatment on synovial tissue. Ann Rheum Dis. 2009;68(8):1303-1309.[7]Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11(8):519-531.AcknowledgementsWe would like to thank all participating patients and Tom de Groot for his expertise in evaluating neutrophils by flow cytometry.Disclosure of InterestsAoife M O’Byrne: None declared, J.W. Bolt: None declared, Chaja van Ansenwoude: None declared, J.F. Semmelink: None declared, Mario Maas: None declared, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Advisory board: Abbvie, Eli Lily, Novartis, UCB, Grant/research support from: Novartis, Janssen, UCB, Eli Lilly, Lisa van Baarsen: None declared